Bioresorbable Vascular Scaffolds Restenosis

JACC: CARDIOVASCULAR INTERVENTIONS

VOL. 10, NO. 18, 2017

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 1936-8798/$36.00

PUBLISHED BY ELSEVIER

http://dx.doi.org/10.1016/j.jcin.2017.08.025

EDITORIAL COMMENT

Bioresorbable Vascular Scaffolds Restenosis Pathophysiology and Predictors* Fernando Alfonso, MD, PHD, Javier Cuesta, MD

B

ioresorbablve vascular scaffolds (BVS) were

exists regarding the underlying mechanisms of BVS

introduced a decade ago with the aim of over-

ISR (6–14).

coming some limitations of metallic drug-

eluting stents (DES) (1–3). BVS allow effective drug delivery with temporary scaffolding of the treated segment but eventually completely disappear from the vessel wall once their goal has been accomplished. BVS hold the promise of restoring coronary vasomotion, sealing vulnerable coronary plaques, and allowing the vessel lumen to benefit from plaque

regression and adaptive remodeling (1–3). However, meeting most of these expectations has proved to be more challenging than initially anticipated (1–3). Indeed, despite the favorable results of most early studies, safety and efficacy concerns arose when the information from the complete set of controlled studies with adequate long-term clinical follow-up became available (1–3). Aggregate analyses of these

PRESENT STUDY In this issue of JACC: Cardiovascular Interventions, Polimeni et al. (15) report on a study in which they sought to assess the incidence, clinical presentation, and predictors of BVS ISR. In this retrospective singlecenter study, including 657 consecutive patients treated with 883 BVS, careful clinical follow-up (median 3 years) revealed the occurrence of clinical BVS ISR in 49 lesions in 41 patients. The incidence of ISR was 2.4%, 6.0%, and 9.0% at 12, 24, and 36 months, respectively. In most cases BVS ISR presentation was benign (stable symptoms or incidental finding), and only 19% of patients presented with acute coronary syndromes. One-half of these lesions had a nonfocal

studies demonstrated a low yet statistically significant higher risk for thrombosis compared with newgeneration DES (1–3). Moreover, poorer acute and late angiographic results were also demonstrated (2). In some trials, a higher rate of in-stent restenosis (ISR) was found. Recent meta-analyses suggested that compared with new-generation DES, BVS are associated with a 40% increase in ischemia-driven target lesion revascularization (3). Although much attention has been paid to identifying the pathophysiology of BVS thrombosis because of its dreadful clinical consequences (4,5), currently only limited information

SEE PAGE 1819

angiographic pattern. Although the potential influence of lesion length was not presented, long BVS and small vessels were associated with higher recurrence rates.

On

optical

coherence

tomography

(OCT)

(available in 27 lesions), the predominant underlying substrate was homogeneous high-intensity neointima. Only 4 cases showed neointima with lowintensity areas, but none was considered suggestive of neoatherosclerosis. Interestingly, images suggestive of BVS fracture were very frequent at follow-up (35% in patients without ISR vs. 61% in those developing ISR). Malapposition and evagination were less frequently found in patients with ISR. Importantly,

*Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology. From the Department of Cardiology, Hospital Universitario de La

prior revascularization, diabetes, type B2 or C lesions, and implantation technique emerged as independent predictors of BVS ISR. Notably, device oversizing or

Princesa, Madrid, Spain. Both authors have reported that they have no

undersizing and final residual stenosis predicted an

relationships relevant to the contents of this paper to disclose.

increased risk for ISR. Eventually, most patients

Alfonso and Cuesta

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 18, 2017 SEPTEMBER 25, 2017:1828–31

Restenosis of Bioresorbable Scaffolds

F I G U R E 1 Optical Coherence Tomographic Findings in Patients With Bioresorbable Vascular Scaffold In-Stent Restenosis

(A) Underexpanded bioresorbable vascular scaffold (BVS) with bright homogeneous neointimal proliferation. (B) Severely underexpanded BVS showing distorted struts (arrows) within a high-backscatter uniform neointima. (C) Glistening superficial neointima overlying dark areas with diffuse borders (plus signs). (D) Massive tissue obstruction in a nicely expanded BVS. Notice a layered heterogeneous pattern with peristrut low-intensity areas (plus signs). (E) The tissue obstructing this BVS shows dark areas with sharply delineated edges (plus signs). (F) Highly heterogeneous tissue encompassing some punctuated bright areas casting dorsal shadowing (arrow). In all these cases of BVS in-stent restenosis (time to restenosis 132 to 649 days), the “black boxes” corresponding to the BVS struts are still clearly recognizable. Asterisk denotes wire artifact.

(67%) were treated with DES, and midterm clinical

vessels, major bifurcations, vein grafts, and ostial and

outcomes were favorable (15).

ISR lesions.

This investigation, the largest series currently

Second, OCT revealed that the principal mecha-

available focusing on BVS ISR, is of major interest.

nism of BVS ISR was severe neointima proliferation.

Discussing some methodological issues and study

These findings suggest progressive growth of benign

findings appears warranted to disclose what the study

fibrotic neointima. Conversely, other studies using

adds to current knowledge.

OCT have found that neoatherosclerosis plays a major

First, although systematic late angiographic eval-

role in this setting (14). Time to BVS ISR presentation

uation is necessary to ascertain the true incidence of

might be implicated. Different criteria to define neo-

ISR, and this was not performed in the present study,

atherosclerosis could also help explain the differ-

the analysis of “clinical” ISR is highly relevant.

ences. This elusive pathological substrate might be

Moreover, the present study, describing the incidence

overestimated when liberal definitions are selected.

of clinical ISR in a complex all-comers clinical setting,

Alternatively, some images from the present study,

may be better suited to understand the efficacy of

depicting large low-intensity areas obscuring most

BVS in relatively unselected patients treated in

BVS struts (15), might have been interpreted as neo-

everyday clinical practice than data coming from

atherosclerosis by other investigators (Figure 1).

controlled studies including highly selected patients

Third, stent underexpansion remains the most

and mandated angiographic surveillance. Neverthe-

robust predictor of ISR and thrombosis, even with

less, even in this study, the use of BVS was discour-

new-generations DES (16). In this study, patients with

aged in patients with tortuous or heavily calcified

BVS ISR had significantly smaller minimal scaffold

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Alfonso and Cuesta

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 18, 2017 SEPTEMBER 25, 2017:1828–31

Restenosis of Bioresorbable Scaffolds

T A B L E 1 Pathophysiology of Bioresorbable Vascular

Scaffold Restenosis

1. Excessive neointimal proliferation* 2. Neoatherosclerosis
Stable (gradual, progressive development)
Complicated (ruptured capsule with associated thrombosis) 3. BVS underexpansion with preserved structure 4. Small target vessel (#2.25 mm; strut overcrowding) 5. BVS structural changes
Acute B BVS damage during implantation or inappropriate overexpansion (BVS fracture) B Secondary to insufficient radial strength (acute recoil)
Late: related to programmed bioresorption B Within the vessel wall: loss of structural support - Initial configuration preserved - With displacement or disruption (late recoil); loss of alignment or circularity B With disrupted elements floating within the lumen (malapposition) - Initial configuration preserved - Modified spatial configuration; loss of alignment or circularity, overhung struts (BVS “dismantling”) 6. “Delayed” BVS resorption; very late (>3 to 4 years) persistence of structural elements in the vessel wall

been most valuable. Importantly, dismantling have been associated with an abnormal bioresorption process, leading to adverse clinical events (5,10). Last but not least, an “optimal technique” for BVS implantation was defined as 1:1 pre-dilatation and post-dilation with noncompliant balloons appropriately sized (using quantitative coronary angiography) for the reference vessel diameter (ranging from 2.5 to 3.5 mm) and a final residual diameter stenosis <20%. This is appealing, as patients treated using this strategy obtained better clinical outcomes. Optimism, however, should be cautiously tempered, because studies indicate that even with the use of optimal implantation techniques, BVS might still show higher rates of device failure compared with new-generation DES.

DISTINCT PERSPECTIVES ON BVS FAILURE

7. Resistance to the antiproliferative drug

Multiple mechanisms potentially leading to BVS ISR

8. Disease in adjacent coronary segments not covered by the BVS (5-mm edges)
Disease progression (several plaque types) at the initially untreated BVS edges
Progression of atherosclerotic plaque at segments treated (injured) but uncovered by the BVS (“geographic miss”)
Overlap failure (“gap”) between 2 separate BVS

have been described (6–14) (Table 1). Most of these have been also implicated in BVS thrombosis (4,5) and in ISR after DES implantation (16). However, some specific characteristic inherent to the polymeric BVS could promote distinct pathophysiologic mechanisms.

9. Excessive overlap of 2 adjacent BVS (long lesions†)

These would include: 1) the thick struts, required to

10. Associated with BVS-related aneurysm formation

achieve the necessary initial radial force, generate

Several mechanisms may be involved in the same patient. Classic factors such as diabetes (*) and lesion length (†) always emerge as risk factors for restenosis independently of the selected treatment. Modified with permission from Alfonso and García-Guimaraes (6). BVS ¼ bioresorbable vascular scaffold.

adverse rheological profiles and uneven shear stress, stimulating neointimal proliferation; 2) the progressive loss of structural support during the bioresorption process might favor BVS collapse and vessel recoil; 3) the complete disappearance of the BVS opens a brand new scenario in which the vessel may either keep

areas at follow-up compared with patients without

healing (with some studies suggesting plaque regres-

ISR. Unfortunately, a detailed analysis of BVS

sion), or, alternatively, the underlying disease may

expansion by OCT was not provided, as this param-

progress (neoplaque formation) without any struc-

eter was only assessed using the angiographic

tural barrier preventing lumen encroachment. How-

reference vessel diameter. Furthermore, the lack of

ever, the prevalence and characteristics of restenosis

OCT at the time of BVS implantation prevents dis-

occurring in this later scenario (complete resorption

missing the potential influence of early or late BVS

without any remaining scaffold structure) have not yet

recoil on these findings (8).

been established and will require longer follow-up and

Fourth, the presence of images suggestive of BVS

detailed intracoronary imaging studies.

fracture (stacked, overhung, or disrupted intraluminal struts) was higher than in previous studies

CLOSING REMARKS

(14). Indeed, two-thirds of patients with ISR showed features consistent with BVS fracture. Nevertheless,

The study of Polimeni et al. (15) provides novel

the investigators fail to discuss in depth the potential

insight into the causes and predictors of BVS failure

meaning of these striking findings. Some images

that may help inform treatment decisions in clinical

suggesting fracture might actually correspond to

practice. Whether the risk for BVS ISR may be

structural discontinuities resulting from the pro-

significantly reduced by avoiding particularly chal-

grammed BVS dissolution process. In this regard,

lenging lesions, by the use of specific implantation

additional morphological information (late structural

techniques, or by the systematic use of intracoronary

discontinuity vs. true BVS “dismantling”) would have

imaging

(especially

to

tackle

underexpansion)

Alfonso and Cuesta

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 18, 2017 SEPTEMBER 25, 2017:1828–31

Restenosis of Bioresorbable Scaffolds

remains controversial (6). Larger trials with extended

at

follow-up are essential to expand our knowledge and

compared with new-generation DES.

least

similar

long-term

safety

and

efficacy

improve treatment of patients with BVS ISR. Whether the risk for BVS thrombosis and ISR will be mitigated

ADDRESS FOR CORRESPONDENCE: Dr. Fernando

with the advent of device iterations also remains

Alfonso, Department of Cardiology, Hospital Uni-

speculative. The potential benefits of complete

versitario de La Princesa, Universidad Autónoma de

restoration

be

Madrid, Instituto de Investigación Sanitaria Prin-

contemplated with healthy scientific skepticism until

cesa, Diego de León 62, Madrid 28006, Spain. E-mail:

compelling clinical evidence confirms that BVS offer

[email protected].

of

vascular

physiology

should

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Incidence, clinical presentation, and predictors of clinical restenosis in coronary bioresorbable scaffolds. J Am Coll Cardiol Intv 2017;10: 1819–27. 16. Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. J Am Coll Cardiol 2014;63:2659–73.

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KEY WORDS bioresorbable vascular scaffold, drug-eluting stent(s), in-stent restenosis, optical

Intervention 2015;10:1288–98.

coherence tomography

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